{"doi":"10.17615/fxn0-az38","title":"Wilms Tumor Gene on X Chromosome (WTX) Inhibits Degradation of NRF2 Protein through Competitive Binding to KEAP1 Protein","abstract":"Background: KEAP1 is a ubiquitin ligase adaptor that promotes the ubiquitination and degradation of NRF2, a transcription factor that drives the antioxidant response.Results: Wilms tumor gene on the X chromosome (WTX) stabilizes NRF2 by competing with NRF2 for binding to KEAP1.Conclusion: WTX regulates the antioxidant response.Significance: This study reveals a novel regulatory mechanism governing the antioxidant response.WTX is a tumor suppressor protein that is lost or mutated in up to 30% of cases of Wilms tumor. Among its known functions, WTX interacts with the β-transducin repeat containing family of ubiquitin ligase adaptors and promotes the ubiquitination and degradation of the transcription factor β-catenin, a key control point in the WNT/β-catenin signaling pathway. Here, we report that WTX interacts with a second ubiquitin ligase adaptor, KEAP1, which functions to regulate the ubiquitination of the transcription factor NRF2, a key control point in the antioxidant response. Surprisingly, we find that unlike its ability to promote the ubiquitination of β-catenin, WTX inhibits the ubiquitination of NRF2. WTX and NRF2 compete for binding to KEAP1, and thus loss of WTX leads to rapid ubiquitination and degradation of NRF2 and a reduced response to cytotoxic insult. These results expand our understanding of the molecular mechanisms of WTX and reveal a novel regulatory mechanism governing the antioxidant response.","journal":"UNC Libraries","year":2020,"id":117888,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9638,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":526891,"name":"Feng Yan","orcid":"0000-0001-7385-6334","position":1,"is_corresponding":false},{"id":463179,"name":"James M. Davison","orcid":"0000-0003-2453-7227","position":2,"is_corresponding":false},{"id":250992,"name":"Richard G. James","orcid":"0000-0002-2302-7367","position":3,"is_corresponding":false},{"id":422008,"name":"David W. Dawson","orcid":"0000-0002-0215-5861","position":4,"is_corresponding":false},{"id":549445,"name":"Scott A. Houck","orcid":null,"position":5,"is_corresponding":false},{"id":18212,"name":"Michael B. Major","orcid":"0000-0002-6753-8513","position":6,"is_corresponding":false},{"id":79571,"name":"Randall T. Moon","orcid":"0000-0002-9352-1408","position":7,"is_corresponding":false},{"id":79563,"name":"Nathan D. Camp","orcid":"0000-0002-1216-5262","position":8,"is_corresponding":false},{"id":6649,"name":"Ning Zheng","orcid":"0000-0002-1039-1581","position":9,"is_corresponding":false},{"id":548595,"name":"Xiaobo Tang","orcid":"0000-0001-6097-6935","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:54.951170Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}